The major aim of this project is to develop new magnetic resonance (MR) "spin tagging" approaches for imaging cerebral blood flow (CBF) in humans, and to apply these approaches to study physiological and pharmacological dysfunction in psychiatric patients. The new MR approaches use classical tracer theory based on the Kety-Schmidt equation, but instead of using radioactive tracers they use perturbed magnetic spin states of stable isotopes. Previous work in this project identified a number of major problems that had precluded the calculation of quantitative cerebral blood flow values in humans, and developed theoretical methodological approaches for overcoming these problems. During the last year the CBF imaging approaches have been validated using a combined MR/PET study, and have been applied to study regional increases in cerebral blood flow in motor and cognitive activation paradigms. For example, the average increase in CBF in primary sensorimoter cortex during motor tasks was 60 + - 10 cc/100g/min (91%), while the average increase in CBF in prefrontal cortex during working memory tasks was 22 +/- 5 cc/100g/min (23%). Work in the upcoming two years will focus on the study of regional cerebral dysfunction in psychiatric patients.